Synergic Effects of CD40 and CD86 Silencing in Dendritic Cells on the Control of Allergic Diseases

Suzuki, Motohiko; Yokota, Makoto; Matsumoto, Tomo; Ozaki, Shinya

doi:10.1159/000489862

Cited by 9 publications

(13 citation statements)

References 20 publications

(36 reference statements)

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“…DCs were generated from bone marrow progenitor cells of 6-to 8-week-old male BALB/c mice (Japan SLC, Shizuoka, Japan), as previously reported. 11 , 19 , 20 , 21 Briefly, bone marrow cells were flushed from the femurs and tibias and cultured. DCs (CD40-silenced DCs) were transfected with siRNA against CD40 (CD40 siRNA, UUCUCAGCCCAGUGGAACA).…”

Section: Methodsmentioning

confidence: 99%

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Intranasal administration of regulatory dendritic cells is useful for the induction of nasal mucosal tolerance in a mice model of allergic rhinitis

Suzuki

Yokota

Kanemitsu

et al. 2020

World Allergy Organization Journal

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Background Intranasally administered dendritic cells (DCs) migrate into blood and thymus to induce immune responses. Regulatory dendritic cells (DCs) are also useful agents for allergy control. However, to the best of our knowledge, the effects of intranasal administration of regulatory DCs on allergy have not been reported until now. Therefore, we examined the effects of intranasal route of administration of CD40-silenced DCs on allergic responses and compared these with the effects of other administration routes, based on our previous findings on the inhibitory effects of CD40-silenced DCs on allergic responses. Methods Mice with allergic rhinitis were treated intranasally, subcutaneously, intraperitoneally, or intravenously with CD40-silenced ovalbumin (OVA)-pulsed DCs that were transfected with CD40 siRNAs and pulsed with OVA antigen. The effects of these DCs on allergic reactions and symptoms were estimated. Results Intranasal, subcutaneous, intraperitoneal, or intravenous administration of OVA-pulsed CD40-silenced DCs inhibited allergic responses and symptoms in mice. Furthermore, intranasal administration of OVA-pulsed CD40-silenced DCs significantly reduced allergic symptoms and the number of eosinophils in the nasal mucosa compared with subcutaneous, intraperitoneal, or intravenous administration of these DCs. Intranasal administration of OVA-pulsed CD40-silenced DCs resulted in significantly up-regulated IL-10, IL-35, and Foxp3 expression, and enhanced the percentage of CD11c + CD40 − and CD4 + CD25 + cells within the cervical lymph nodes compared to subcutaneous, intraperitoneal, or intravenous routes of administration. Conclusions We believe that this is the first report to demonstrate that regulatory DCs infiltrate into the cervical lymph nodes after intranasal administration of these cells and that intranasal administration of regulatory DCs is more effective for the induction of tolerance in the nasal mucosa than subcutaneous, intraperitoneal, or intravenous administration.

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Section: Methodsmentioning

confidence: 99%

“…OVA-specific T-cell responses were estimated as previously reported. 21 Lymphoid cells (2 × 10 6 cells/mL) from the cervical lymph nodes and spleen were cultured with OVA (100 μg/mL) at 37 °C for 72 h, after which the culture supernatants were collected.…”

Section: Methodsmentioning

confidence: 99%

Intranasal administration of regulatory dendritic cells is useful for the induction of nasal mucosal tolerance in a mice model of allergic rhinitis

Suzuki

Yokota

Kanemitsu

et al. 2020

World Allergy Organization Journal

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“…13,14 Transfection of CD40 siRNA (1 mg) and CD86 siRNA (1 mg) into DCs was also performed as previously described. 8,15,16 Immunization and Treatment CD40-silenced OVA B cells (5 Â 10 6 cells/mouse), CD86silenced OVA B cells (5 Â 10 6 cells/mouse), CD40-/ CD86-silenced OVA B cells (5 Â 10 6 cells/mouse), CD40-/CD86-silenced OVA DCs (5 Â 10 6 cells/mouse), control B cells (CD40-expressing B cells, 5 Â 10 6 cells/ mouse), or phosphate-buffered saline (PBS) alone were injected intravenously into 7-week-old male BALB/c mice on day 1. These mice were sensitized with intraperitoneal OVA (10 lg) and 2 mg Al (OH) 3 on days 2 and 16.…”

Section: Sirna and Gene Silencingmentioning

confidence: 99%

“…7 We also reported that CD40-silenced B cells inhibited allergic responses and symptoms. 8 However, more potent therapies are needed.…”

Section: Introductionmentioning

confidence: 99%

“…9 We previously showed synergic effects of CD40 and CD86 silencing in DCs on the control of allergic diseases. 8 However, it is controversy whether synergic effects of CD40 and CD86 silencing in B cells exists on the control of allergic diseases, and whether CD40-and CD86-silenced B cells has more potent inhibitory effects on allergic symptoms than CD40-and CD86-silenced DCs.…”

Section: Introductionmentioning

confidence: 99%

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Impacts of CD40- and CD86-Silenced Antigen-Specific B Cells on the Control of Allergies

Suzuki

Matsumoto

Toyoda

et al. 2019

Am J Rhinol�Allergy

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Background We previously reported that CD40-silenced B cells inhibited allergic responses and symptoms. However, more potent therapies are needed. To our knowledge, the effects of CD86-silenced B cells and synergic effects of gene silencing in B cells by 2 small interfering RNAs (siRNAs) on allergic disease control have not been reported. Objective To investigate the effects of CD86-silenced B cells and synergic effects of gene silencing in B cells on allergic responses and symptoms. Methods Mice were treated with CD40- and/or CD86-silenced B cells transfected with siRNAs and pulsed with ovalbumin (OVA). And the effects of these B cells were estimated. Results CD86-silenced OVA-pulsed B cells significantly inhibited OVA-induced allergies. Treatment with CD40-/CD86-silenced OVA-pulsed B cells led to a significantly fewer sneezes and nasal rubbing movements, as well as lower OVA-specific immunoglobulin E (IgE) levels, than that with CD40-silenced or CD86-silenced OVA-pulsed B cells alone. These inhibitory effects were observed prior to sensitization as well as after the establishment of allergic rhinitis. CD40-/CD86-silenced OVA-pulsed B cells did not inhibit keyhole limpet hemocyanin-induced allergies. CD40-/CD86-silenced OVA-pulsed B cells also significantly inhibited allergic symptoms and OVA-specific IgE level in sera compared with CD40-/CD86-silenced OVA-pulsed dendritic cells (DCs). In addition, CD19+CD40− B cells significantly increased in the nasal tissue after intravenous administration of these cells. Furthermore, CD40-/CD86-silenced B cells inhibited allergic symptoms caused by Cry j 1, a major aeroallergen of Japanese cedar pollen, and Cry j 1-specific IgE in sera. Conclusion This study showed, for the first time, that siRNA-induced CD86-silenced B cells significantly inhibited allergic responses and symptoms antigen-specifically, and that siRNA-induced CD40-/CD86-silenced antigen-specific B cells are a more useful antigen-specific therapy than CD40- or CD86-silenced B cells alone for the control of allergies. Furthermore, it was shown that CD40-/CD86-silenced B cells have stronger inhibition of IgE production and allergic symptoms than CD40-/CD86-silenced DCs.

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Hyperbaric oxygen treatment on keloid tumor immune gene expression

Chun-hu

Shan

Liu

et al. 2021

Chinese Medical Journal

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Background: Hyperbaric oxygen treatment (HBOT) has been demonstrated to influence the keloid recurrence rate after surgery and to relieve keloid symptoms and other pathological processes in keloids. To explore the mechanism of the effect of HBOT on keloids, tumor immune gene expression and immune cell infiltration were studied in this work. Methods: From February 2021 to April 2021, HBOT was carried out on keloid patients four times before surgery. Keloid tissue samples were collected and divided into an HBOT group (keloid with HBOT before surgery [HK] group, n = 6) and a non-HBOT group (K group, n = 6). Tumor gene expression was analyzed with an Oncomine Immune Response Research Assay kit. Data were mined with R package. The differentially expressed genes between the groups were compared. Hub genes between the groups were determined and verified with Quantitative Real-time PCR. Immune cell infiltration was analyzed based on CIBERSORT deconvolution algorithm analysis of gene expression and verified with immunohistochemistry (IHC). Results: Inflammatory cell infiltration was reduced in the HK group. There were 178 upregulated genes and 217 downregulated genes. Ten hub genes were identified, including Integrin Subunit Alpha M ( ITGAM ), interleukin ( IL )- 4 , IL-6 , IL-2 , Protein Tyrosine Phosphatase Receptor Type C ( PTPRC), CD86 , transforming growth factor ( TGF), CD80 , CTLA4 , and IL-10 . CD80 , ITGAM , IL-4 , and PTPRC with significantly downregulated expression were identified. IL-10 and IL-2 were upregulated in the HK group but without a significant difference. Infiltration differences of CD8 lymphocyte T cells, CD4 lymphocyte T-activated memory cells, and dendritic resting cells were identified with gene CIBERSORT deconvolution algorithm analysis. Infiltration levels of CD4 lymphocyte T cell in the HK group were significantly higher than those of the K group in IHC verification. Conclusion: HBOT affected tumor gene expression and immune cell infiltration in keloids. CD4 lymphocyte T cell, especially activated memory CD4 + T, might be the key regulatory immune cell, and its related gene expression needs further study.

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Synergic Effects of CD40 and CD86 Silencing in Dendritic Cells on the Control of Allergic Diseases

Cited by 9 publications

References 20 publications

Intranasal administration of regulatory dendritic cells is useful for the induction of nasal mucosal tolerance in a mice model of allergic rhinitis

Intranasal administration of regulatory dendritic cells is useful for the induction of nasal mucosal tolerance in a mice model of allergic rhinitis

Impacts of CD40- and CD86-Silenced Antigen-Specific B Cells on the Control of Allergies

Hyperbaric oxygen treatment on keloid tumor immune gene expression

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